Journal Article

FZJ-2023-02646

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Vesicular glutamate transporters are H+-anion exchangers that operate at variable stoichiometry

Kolen, B.FZJ* ; Borghans, B.FZJ* ; Kortzak, D.FZJ* ; Lugo, V.FZJ* ; Hannack, C. ; Guzman, R.FZJ* ; Ullah, G. ; Fahlke, C. (Corresponding author)FZJ*

2023
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-023-38340-9  doi:10.34734/FZJ-2023-02646

Abstract: Vesicular glutamate transporters accumulate glutamate in synaptic vesicles, where they also function as a major Cl- efflux pathway. Here we combine heterologous expression and cellular electrophysiology with mathematical modeling to understand the mechanisms underlying this dual function of rat VGLUT1. When glutamate is the main cytoplasmic anion, VGLUT1 functions as H+-glutamate exchanger, with a transport rate of around 600 s−1 at −160 mV. Transport of other large anions, including aspartate, is not stoichiometrically coupled to H+ transport, and Cl- permeates VGLUT1 through an aqueous anion channel with unitary transport rates of 1.5 × 105 s−1 at −160 mV. Mathematical modeling reveals that H+ coupling is sufficient for selective glutamate accumulation in model vesicles and that VGLUT Cl- channel function increases the transport efficiency by accelerating glutamate accumulation and reducing ATP-driven H+ transport. In summary, we provide evidence that VGLUT1 functions as H+-glutamate exchanger that is partially or fully uncoupled by other anions.

Note: This workwas supported by the Deutsche Forschungsgemeinschaft (GermanResearch Foundation) to Ch.F. (FA 301/15–2) as part of Research UnitFOR 2518, DynIon; to Ch.F. and G.U. as part of the Research Unit FOR2795, to REG (GU 2042/2-1), and by the NIH to G.U. (R01 AG053988).

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Contributing Institute(s):

1. Molekular- und Zellphysiologie (IBI-1)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2023

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